Issues
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Cover image
Cover Image
Cover: The ciliary zonule, a network of radial fibers (red), projects from the folded surface of the ciliary epithelium and centers the lens of the eye (violet sphere) on the optical axis. See article by Jones et al. (dmm037283). Cover image is licensed under a Creative Commons Attribution 4.0 International license.
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FIRST PERSON
AT A GLANCE
Generating mouse models for biomedical research: technological advances
Summary: Newer molecular technologies to precisely and efficiently manipulate the mammalian genome are enabling the production of more scientifically valuable animal models.
REVIEW
Transgenic and physiological mouse models give insights into different aspects of amyotrophic lateral sclerosis
Summary: This Review compares two key types of amyotrophic lateral sclerosis (ALS) mouse models: transgenic mice and those that express genes at physiological levels. We explore the advantages of each type for studying pathomechanisms, to understand what they can teach us about ALS.
RESEARCH ARTICLES
Yeast-model-based study identified myosin- and calcium-dependent calmodulin signalling as a potential target for drug intervention in chorea-acanthocytosis
Summary: Using the vps13Δ strain, a yeast model of the neurodegenerative disorder chorea-acanthocytosis, we found that its defects can be overcome by reduction of calcineurin activity and/or type-I-myosin activation.
Targeted deletion of fibrillin-1 in the mouse eye results in ectopia lentis and other ocular phenotypes associated with Marfan syndrome
Summary: Targeted knockout of Fbn1 in the ciliary epithelium of the mouse eye undermines the structural and biomechanical integrity of the ciliary zonule and results in an ectopia lentis phenotype.
Modelling pancreatic β-cell inflammation in zebrafish identifies the natural product wedelolactone for human islet protection
Summary: A model of islet inflammation in zebrafish exhibits functional β-cell silencing and a lack of glucose responsiveness. A natural compound that rescues the glucose defect in zebrafish can protect human islets from inflammation.
An exonic splicing enhancer mutation in DUOX2 causes aberrant alternative splicing and severe congenital hypothyroidism in Bama pigs
Summary: Here, we show that an exonic splicing enhancer variant in DUOX2 (c.1226 A>G) causes aberrant splicing of DUOX2 transcripts, resulting in lower H2O2 production, to cause severe congenital hypothyroidism in Bama pigs.
The ubiquitin ligase HECTD1 promotes retinoic acid signaling required for development of the aortic arch
Editor's choice: The HECTD1 ubiquitin ligase is a novel modulator of retinoic acid signaling during aortic arch development and provides a model for complex interactions underlying variations in aortic arch development.
Photoreceptor degeneration in microphthalmia (Mitf) mice: partial rescue by pigment epithelium-derived factor
Summary: This study reveals that the MITF-PEDF pathway plays a critical role in RPE homeostasis and that simple eye drops of a PEDF 17-mer peptide can partially prevent Mitf deficiency-associated retinal degeneration in mice.
SUMOylation by SUMO2 is implicated in the degradation of misfolded ataxin-7 via RNF4 in SCA7 models
Summary: In spinocerebellar ataxia type 7, SUMOylation contributes to the clearance of mutant ATXN7. SUMO2-modified ATXN7 interacts with the SUMO-dependent ubiquitin ligase RNF4, which polyubiquitinates ATXN7, promoting its proteasomal degradation.
PREPRINT HIGHLIGHTS
Call for papers – In Vitro Models of Human Disease to Inform Mechanism and Drug Discovery

We invite you to submit your latest research to our upcoming special issue: In Vitro Models of Human Disease to Inform Mechanism and Drug Discovery, coordinated by DMM Editor Vivian Li (The Francis Crick Institute, London, UK), alongside Guest Editors Austin Smith (University of Exeter, UK) and Joseph Wu (Stanford University School of Medicine, USA).The deadline for submitting articles is 6 October 2025.
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